Project Objectives

• Learn the method for culturing pancreatic neuroendocrine tumour (PNET) patient‑derived organoids (PDOs) from the Host Lab (Keio University) and establish stable, long‑term PDO cultures at the Home Lab (University of Bern).
• Confirm PDOs as a superior model for image-based phenotyping and functional assessment of PNET biology.
• Replace mouse models of PNETs with PDOs and develop novel PDOs from patient material.
• Create a PDO biobank which covers the range of PNETs, to be shared with the global network of PNET researchers and other external parties.

3Rs Impact

• Eliminates the need for xenograft ADR studies, which reduces animal use (for example, testing the ADR timeline for one drug using the PDO model would save ~56 tumour-xenografted mice at the University of Bern alone).
• Avoids the use of high‑severity genetically modified mouse models required for ADR (SD3).
• Improves the reproducibility, cost‑effectiveness, and human-relevance of PNET research.
• Supports a longer‑term shift toward fully PDO‑based research for PNETs.

Background

Pancreatic neuroendocrine tumour (PNET) research is limited by a lack of human-relevant model systems. Most studies rely on genetically modified or xenograft mouse models, which require months of monitoring, large numbers of animals, and offer limited suitability for automation or high‑throughput drug testing.

At the Home Lab (Institute of Tissue Medicine and Pathology, University of Bern) ongoing research focuses on the epigenetic and metabolic changes in PNET progression, the mechanisms underlying acquired drug resistance (ADR), and the development of new patient‑derived 3D models. However, only a few authentic human PNET cell lines exist, which restricts this mechanistic and therapeutic work.

The Host Lab (Keio University) established the first patient‑derived organoids (PDOs) for PNETs, and these are suited for long-term culture and assessment, capture human disease features, and can be genetically manipulated. Learning the techniques to culture PNET PDOs will provide the University of Bern with a scalable solution for functional assessment of PNET progression and drug‑response analysis, while also helping to replace animal‑based ADR studies.